Figure 4: Ezh2 ablation in Tyr::N-Ras ^Q61K Ink4a ^−/− mice prevents skin melanoma formation.

(a,b) Mouse genotypes (a) and strategy (b) used to analyze the effect of conditional Ezh2 ablation on dermal hyperplasia and melanoma formation in Tyr::N-Ras^Q61K Ink4a^−/− mice. (c) Macroscopic pictures of a control and a cKO littermate at 5 months post Ezh2 ablation. (d) Immunofluorescent staining for Dct on trunk skin sections 2 weeks after conditional Ezh2 ablation to quantify dermal hyperplasia size. (e) Immunofluorescent staining for Sox10 (control) or β-Gal (cKO) and Ki67 on trunk skin sections 5 months after conditional Ezh2 ablation to quantify proliferation rates. White arrowhead, Sox10-positive/Ki67-positive cell; white open arrowheads, Sox10- or β-Gal-positive/Ki67-negative cells. (f) H&E staining on trunk skin sections of control and cKO mice at day of sacrifice to quantify skin melanoma numbers. (g) Kaplan–Meier curves comparing melanoma-specific survival after conditional Ezh2 ablation. For cKO mice, only recombined skin melanomas were taken into count as in (Supplementary Fig. 3e). E, epidermis; HF, hair follicle; H&E, haematoxylin and eosin. Data are represented as median±100% range of n≥20 interfollicular areas, three animals per group (d), mean±s.e.m. of n=3 (e), mean±s.e.m. of n=32 (control), n=23 (cKO) (f). P values calculated with unpaired Student’s t-test (d–f), log-rank (Mantel–Cox) test (g). Scale bars, 50 μm (d,e), 500 μm (f).